One limitation of tissue engineering and in vitro tissue growth strategies has been the challenge of recapitulating the natural structures of tissues and organs. In order to grow even the simplest of tissues, an exquisite balance of a complex mixture of growth factors, signaling molecules, nutrients, extracellular matrix scaffolds and mechanical forces that vary over time must be achieved, or cells will fail to organize correctly into tissue and organ structures. Alternatively, removing existing tissue or organ structures from a subject in order to study or propagate the tissue ex vivo can cause damage to the tissues and reestablishing the proper flow of nutrients into the tissue in culture or during transport for transplantation has proven difficult.
For example, hematopoietic stem cells, useful as a source of therapeutic bone marrow material for transplantation or for manufacturing differentiated blood cell replacements (e.g. erthyrocytes, platelets, or leukocytes) have been intractable to in vitro culture. Some investigators have attempted to culture and expand hematopoietic stem cells (HSCs) in vitro, but long-term engraftment and host hematopoietic reconstitution from cultured HSCs has been extremely inefficient (Csaszar, E. et al. Cell Stem Cell 10, 218-229 (2012); Boitano, A. E. et al. Science 329, 1345-348 (2010); Cook, M. M. et al. Tissue Eng. 18, 319-328 (2012)). Multi-potent HSCs are difficult to maintain in vitro because they commonly differentiate when removed from the complex bone marrow niche that contains numerous chemical, structural, mechanical and spatial signals that are required for maintenance of their stem cell features (Takagi, M. J. Biosci. Bioeng. 99, 189-196 (2005); Nichols, J. E. et al. Biomaterials 30, 1071-1079 (2009); Maggio, N. D. et al. Biomaterials 32, 321-329 (2011)).
Thus, there is a need for experimental tools and methods that promote assembly of multi-cellular and multi-tissue organ-like structures that exhibit the key structural organization and physiological function of the tissues and organs being modeled and that can survive and remain functional ex vivo.